Tissue sample handling apparatus

ABSTRACT

The invention relates to a tissue sample handling apparatus, in particular for grasping histological samples after infiltration of an embedding medium such as, for example, paraffin, which is characterized in that a sample is immobilizable on the handling apparatus, in particular in a sample holding position, by means of negative pressure.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority of German patent application number 102011 002 194.9 filed Apr. 20, 2011, the entire disclosure of which isincorporated by reference herein.

FIELD OF THE INVENTION

The invention relates to a tissue sample handling apparatus, inparticular for grasping histological samples after infiltration of anembedding medium such as, for example, paraffin.

BACKGROUND OF THE INVENTION

When working with histological samples, in particular when preparinghistological samples in the context of an embedding process for latermicrotoming, it is necessary to be able—in particular between individualprocess steps that as a rule occur at different laboratory locationsand/or in different devices—to grasp the samples and set them down againprecisely and gently. One of the difficulties existing in this contextis that as a general rule the samples are impregnated or at least wettedwith liquids, in particular with liquids that solidify at roomtemperature (for example, paraffin); this greatly complicates handlingwith the aid of mechanical grasping tools, for example tweezers. Inaddition, damage to the sample can occur.

Merely by way of example, mention is made below of a number of processsteps during or between which it may be necessary to grasp samples andset them down again: In the context of the conditioning of histologicalsamples, they are usually first fixed by the application of variouschemicals. The tissue liquid originally present in the natural cavitiesof the sample is thereby replaced, in multiple steps, by a fixingliquid, for example by formalin. In order to convert the fixed samplesinto a state that permits sectioning by means of a microtome, the fixingliquid is replaced by an embedding medium, for example paraffin,gelatin, agar, nitrocellulose, polyester wax, polyethylene glycol, orplastic. During the aforementioned processes, the samples are usuallylocated in a cassette that comprises a plurality of sieve-like openingsso that the chemicals can flow around the samples. A particularembodiment of such a cassette is known, for example, from DE 43 33 118A1. After infiltration of the embedding medium, i.e. for exampleparaffin, into the samples, the excess embedding medium is drained off.The samples can then be removed from the cassette. After this step,however, the samples can be located anywhere within the cassette;because of the paraffin residues adhering to them, for example, thesamples as a rule adhere to the cassette cover, in the cassette cavity,and/or to one another. Stuck-together clumps of samples often forminside the cassette. This complicates reliable, gentle grasping of theindividual samples.

Before further processing, in particular before automated,machine-controlled further processing, of the samples, for examplebefore the further step of casting the samples into a paraffin block(called “blocking”), the sample or samples must be present in isolatedfashion. Detachment and isolation can be performed, for example, usingtweezers; disadvantageously, the risk exists that a sample may bedamaged in this context and possibly even become unusable. Inparticular, the risk exists of unintentionally causing changes to asample that result in artifacts upon later analysis of tissue sectionsof the sample.

DE 20 2009 017 U1 discloses a grasping apparatus for fixing specimensusing a fixing agent. This grasping apparatus comprises a heatable andcoolable probe. Also provided is a temperature regulation unit forheating and cooling the probe and for regulating the temperature of theprobe in a range, the fixing agent exhibiting in that range a change inaggregate state from solid to liquid. Lastly, the paraffin adhering to ahistological sample is used as an adhesion medium that, in the hardened(cooled) state, ensures that the sample to be grasped adheres to theprobe. The sample can be detached again from the probe by subsequentheating of the probe, and thus re-liquefaction of the paraffin. Inpractice, this grasping apparatus is difficult to handle, especiallybecause even liquefied paraffin still exerts an (albeit reduced)adhesive effect between the probe and sample. This, in particular, alsodisadvantageously prevents the use of this grasping apparatus in anautomated system.

SUMMARY OF THE INVENTION

It is therefore the object of the present invention to describe a tissuesample handling apparatus that enables a sample to be grasped andreleased again efficiently, reliably, and gently.

The object is achieved by a tissue sample handling apparatus which ischaracterized in that a sample is immobilizable on the handlingapparatus, in particular in a sample holding position, by means ofnegative pressure.

The invention has the very particular advantage that even samples thatare wetted with a liquid, in particular with an embedding medium such asparaffin, can be grasped and set down again securely and gently, inparticular without damage. Advantageously, the grasping and setting-downoperations function sufficiently securely and reliably that according tothe present invention automated handling of samples, in particular e.g.in the context of an automated sample processing procedure such asautomated blocking, is also made possible with the tissue samplehandling apparatus according to the present invention.

In an advantageous embodiment, a regulating apparatus is provided forregulating the negative pressure. For example, according to the presentinvention the negative pressure can be regulated, preferablyautomatically, as a function of whether or not a sample is immobilizedon the handling apparatus, in particular in a sample holding position.In particular, provision can be made according to the present inventionthat the negative pressure is decreased, preferably automatically, whena sample is aspirated and immobilized on the handling apparatus, inorder to reduce the forces acting on the sample and preferably limitthem to the magnitude that is necessary in order to hold the sample onthe handling apparatus, for example on an aspiration nozzle.

Alternatively or additionally, provision can advantageously be made thata greater negative pressure (lower pressure) is set when no sample isimmobilized on the handling apparatus, for example in order to aspiratea sample securely and reliably. A reduction in negative pressure canoccur, preferably once again automatically, after aspiration.

Especially in the interest of automated sample processing, in aparticularly advantageous embodiment of the tissue sample handlingapparatus according to the present invention a sensor apparatus isprovided which determines whether or not a sample is immobilized on thehandling apparatus, in particular in the sample holding position. Forexample, the sensor apparatus can comprise a pressure sensor thatmeasures the respective current pressure in a chamber or conduitconnected to the aspiration opening. With this embodiment, thedetermination is based on the fact that the pressure in the chamber orconduit drops immediately when the aspiration opening is entirely orpartly closed off by the immobilized sample.

According to the present invention, the pressure sensor can in principlebe arranged in all chambers or conduits in which entire or partialclosure of an aspiration opening by a sample has the effect of a changein pressure.

The tissue sample handling apparatus according to the present inventionpreferably comprises at least one aspiration nozzle. Provision can bemade in particular that the location of the opening of the aspirationnozzle defines the sample holding position. The aspiration nozzle ispreferably coordinated, in terms of the dimension of the aspirationopening, with the size of the samples to be immobilized. It isadvantageous in particular if the aspiration nozzle offers the largestpossible contact area for the sample, in order to distribute the forceacting on the sample over the largest possible contact area.

On the other hand, the opening of the aspiration nozzle must not beselected to be so large that samples are unintentionally sucked inrather than being immobilized. For safety, however, according to thepresent invention a collector apparatus, for example having a collectorsieve, can be provided, for example inside the tissue sample handlingapparatus.

In an advantageous embodiment, provision is therefore made that theaspiration nozzle is exchangeable. An embodiment of the tissue samplehandling apparatus in which different aspiration nozzles, in particularaspiration nozzles having different opening diameters, are attachableand/or that comprises a storage apparatus, in particular a turret orslide magazine, for different aspiration nozzles, in particularaspiration nozzles having different opening diameters, is particularlyadvantageous and particularly quickly adaptable to the respectiveutilization situation. For example, provision can be made that therespectively required aspiration nozzle can be brought into the workingposition, like the objectives of a microscope, by rotating an aspirationnozzle turret.

An advantageous embodiment of the tissue sample handling apparatusaccording to the present invention comprises a separation apparatus forseparating a liquid and/or solid objects, in particular liquid paraffin,out of a gas stream, in particular an air stream, sucked in particularlythrough the aspiration nozzle. In the separation chamber, for example,the paraffin can be separated from a sucked-in paraffin mist.

The separation apparatus can comprise in particular a separation chamberwhich is embodied and arranged in such a way that a liquid sucked inwith a sucked-in gas stream condenses in the separation chamber.

In an embodiment that promotes the condensation procedure particularlyefficiently, the separation chamber is embodied and arranged in such away that the flow velocity of the gas stream decreases upon entry intothe separation chamber and/or upon flowing through the separationchamber. This can be implemented, for example, by the fact that thepassthrough cross section widens. Alternatively or additionally, animpact element, for example an impact panel, and/or a deflection baffleand/or a labyrinth can be provided for the gas stream.

For emptying the separation chamber, provision can advantageously bemade that a liquid sucked in with a gas stream, for example liquidparaffin, and/or a solid object sucked in with a gas stream, are blownout by reversing the flow direction and/or by means of positivepressure. This can be implemented, for example, in that the separationchamber is impinged upon not by a negative pressure but instead by apositive pressure, in particular from a compressed-air conduit.Alternatively or additionally, it is also possible, by reversing theflow direction, to draw out a liquid sucked in with a gas stream and/ora solid object sucked in with a gas stream by means of negativepressure. For this, a negative-pressure conduit could be temporarilyattached to the aspiration nozzle.

Another embodiment according to the present invention, for whichextremely short maintenance and cleaning down times are sufficient,comprises an exchangeable separation chamber. The separation chamber canin particular be advantageously embodied as a disposable containerand/or single-use container

In another embodiment, the separation apparatus contains a centrifugalseparator.

In a very particularly advantageous embodiment, at least one heatingapparatus is provided for heating at least a part of the tissue samplehandling apparatus. This reliably prevents a liquid sucked in with a gasstream from solidifying unintentionally and/or at locations at which thesolidified liquid, for example solidified paraffin, might result in afunctional impairment.

In particular, provision can advantageously be made that at least oneheating apparatus is provided for heating the aspiration nozzle or themultiple aspiration nozzles. Provision can also be made that at leastone heating apparatus is provided for heating conduits, in particulartubing conduits.

The tissue sample handling apparatus according to the present invention[?can] advantageously be embodied for (in particular, automatically)transporting a grasped sample into a predefined or predefinable set-downposition. For this, the tissue sample handling apparatus can comprise,for example, a displacement apparatus, an X-Y-Z manipulator, or a robotarm that can move at least the aspiration nozzle in space, for examplebetween a pickup position and a set-down position.

According to the present invention the tissue sample handling apparatuscan also comprise an image processing system that, preferablyautomatically, detects a sample that is to be picked up and/or aset-down position for a sample to be set down. In particular, provisioncan furthermore be made that an open- or closed-loop control apparatuscontrols in open- and/or closed-loop fashion the position and/or thetravel distance of the sample holding position and/or of the aspirationnozzle, and/or the negative pressure or optionally further parameters,in accordance with the information ascertained by the image processingsystem.

As already mentioned, the tissue sample handling apparatus according tothe present invention can advantageously be part of an automatichandling machine or automatic sample preparation machine.

Further goals, advantages, features, and possible applications of thepresent invention are evident from the description below of anexemplifying embodiment with reference to the drawings. In this context,all features described and/or graphically depicted, independently or inany useful combination, constitute the subject matter of the presentinvention, irrespective of their grouping in the claims or theirinternal references.

BRIEF DESCRIPTION OF THE DRAWING VIEWS

In the drawings:

FIG. 1 schematically shows a tissue sample handling apparatus accordingto the present invention;

FIG. 2 shows a further tissue sample handling apparatus according to thepresent invention having a negative-pressure control system and aseparation apparatus; and

FIG. 3 shows an automatically operating tissue sample handling apparatusaccording to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 schematically shows a tissue sample handling apparatus 1according to the present invention for grasping a histological sample 2and setting it down again.

Tissue sample handling apparatus 1 comprises an aspiration nozzle 3whose aspiration opening 4 defines a sample holding position 5. Sample 2can be immobilized in sample holding position 5 by means of negativepressure.

Aspiration nozzle 3 is connected via a heatable aspiration tube 6 to aseparation apparatus 19, namely to a separation chamber 7. Aspirationtube 6 comprises a heating apparatus 8. Concretely, aspiration tube 6has a heating strip wound around it. This advantageously preventsliquid, such as paraffin, that is sucked in with a gas stream fromalready hardening in aspiration tube 6 and clogging it.

Separation chamber 7 comprises a connector 9 for a conduit 10 by meansof which a negative pressure is generated in separation chamber 7, inaspiration tube 6, and in aspiration nozzle 3. As long as the negativepressure exists, a sample located in sample holding position 5 is heldat the tip of aspiration nozzle 3 by external air pressure. The samplecan be released by switching off the negative pressure.

Separation chamber 7, aspiration tube 6 and aspiration nozzle 3 can alsobe impinged upon via conduit 10 not with negative pressure but instead(in metered fashion) with a positive pressure. The purpose of this is,for example, to blow out the paraffin that has collected in separationchamber 7 or to detach a sample that is adhering stubbornly to theaspiration nozzle, for example because of an adhesive effect of theparaffin.

FIG. 2 shows a further tissue sample handling apparatus 1 according tothe present invention that, in terms of basic function, operates exactlylike tissue sample handling apparatus 1 depicted in FIG. 1. An open- andclosed-loop control apparatus 13, which controls the negative pressurein conduit 10 as a function of the negative pressure in separationchamber 7, is additionally provided. The negative pressure in separationchamber 7 is measured with the aid of a pressure sensor 12 that forwardsmeasurement signals to open- and closed-loop control apparatus 11.

Because the pressure in separation chamber 7 drops immediately whenaspiration opening 4 is closed off entirely or partly by the immobilizedsample 2, open- and closed-loop control apparatus 11 can ascertain, withthe aid of pressure sensor 12, whether or not a sample is immobilized insample holding position 5.

In the interest of gentle treatment of sample 2, open- and closed-loopcontrol apparatus 11 lowers the forces acting on the sample, by reducingthe negative pressure in conduit 10, when a sample 2 is immobilized insample holding position 5. A valve 13 controlled by open- andclosed-loop control apparatus 11 is provided in conduit 10 for thispurpose.

FIG. 3 shows an automatically operating tissue sample handling apparatus1 according to the present invention that is embodied for autonomouslyand automatically grasping a sample 2, for example out of a cassette 14,and setting it down again at another location, for example in anembedding mold 15.

Tissue sample handling apparatus 1 comprises an X-Y-Z manipulator 16that can move at least the aspiration nozzle together with separationchamber 7 freely in space, under the control of a central control system17.

Central control system 17 controls X-Y-Z manipulator 16 as a function ofthe information transmitted to it from an image processing system 18that automatically detects a sample 2 that is to be picked up, and therespective set-down position for a sample 2 that is to be set down.

PARTS LIST

-   -   1 Tissue sample handling apparatus    -   2 Sample    -   3 Aspiration nozzle    -   4 Aspiration opening    -   5 Sample holding position    -   6 Aspiration tube    -   7 Separation chamber    -   8 Heating apparatus    -   9 Connector    -   10 Conduit    -   11 Open- and closed-loop control apparatus    -   12 Pressure sensor    -   13 Valve    -   14 Cassette    -   15 Embedding mold    -   16 X-Y-Z manipulator    -   17 Central control system    -   18 Image processing system    -   19 Separation apparatus

1. A tissue sample handling apparatus (1) for grasping histologicalsamples (2) after infiltration of an embedding medium, wherein a sample(2) is immobilizable on the handling apparatus (1) in a sample holdingposition (5) by means of negative pressure.
 2. The tissue samplehandling apparatus (1) according to claim 1, further comprising a valve(13) for regulating the negative pressure.
 3. The tissue sample handlingapparatus (1) according to claim 1, further comprising a sensorapparatus providing a signal indicating whether or not a sample (2) isimmobilized on the handling apparatus (1) in the sample holding position(5).
 4. The tissue sample handling apparatus (1) according to claim 3,wherein the sensor apparatus comprises a pressure sensor (12) arrangedto measure pressure in a chamber (7) or a conduit (10) of the tissuesample handling apparatus (1).
 5. The tissue sample handling apparatus(1) according to claim 1, further comprising at least one aspirationnozzle (3) in communication with the negative pressure.
 6. The tissuesample handling apparatus (1) according to claim 5, wherein theaspiration nozzle (3) is exchangeable with at least one differentaspiration nozzle (3).
 7. The tissue sample handling apparatus (1)according to claim 6, further comprising a storage apparatus for storinga plurality of different aspiration nozzles (3).
 8. The tissue samplehandling apparatus (1) according to claim 1, further comprising aseparation apparatus (19) for separating a liquid and/or solid objectsout of a gas stream.
 9. The tissue sample handling apparatus (1)according to claim 8, wherein the separation apparatus (19) comprises aseparation chamber (7) embodied and arranged such that a liquid suckedin with a sucked-in gas stream condenses in the separation chamber (7).10. The tissue sample handling apparatus (1) according to claim 8,wherein the separation apparatus (19) comprises a separation chamber (7)having at least one impact element and/or a labyrinth and/or adeflection baffle, which is embodied and arranged in such a way that theflow velocity of the gas stream decreases upon entry into the separationchamber (7) and/or upon flowing through the separation chamber (7). 11.The tissue sample handling apparatus (1) according to claim 8, whereinthe separation apparatus (19) comprises an exchangeable separationchamber (7).
 12. The tissue sample handling apparatus (1) according toclaim 11, wherein the separation chamber (7) is a disposable container.13. The tissue sample handling apparatus (1) according to claim 11,wherein the separation chamber (7) is a single-use container.
 14. Thetissue sample handling apparatus (1) according to claim 8, wherein theseparation apparatus (19) comprises a separation chamber (7), and aliquid sucked in with a gas stream and/or a solid object sucked in witha gas stream is removable from the separation chamber (7) by reversingair flow direction by means of positive pressure.
 15. The tissue samplehandling apparatus (1) according to claim 5, further comprising at leastone heating apparatus (10) for heating at least a part of the tissuesample handling apparatus (1).
 16. The tissue sample handling apparatus(1) according to claim 15, further comprising a separation chamber (7),a conduit (10) connected to the separation chamber (7), and anaspiration tube (6) between the separation chamber (7) and theaspiration nozzle (3), and wherein the at least one heating apparatus(10) is operable to heat at least one of the following: the conduit(10), the aspiration tube (6), and the aspiration nozzle (3).
 17. Thetissue sample handling apparatus (1) according to claim 1, furthercomprising a displacement apparatus whereby the tissue sample handlingapparatus (1) is configured for transporting a grasped sample (2) into apredefined or predefinable set-down position.
 18. The tissue samplehandling apparatus (1) according to claim 17, wherein the tissue samplehandling apparatus (1) comprises an image processing system (18) thatdetects a sample (2) that is to be picked up and/or a set-down positionfor a sample (2) to be set down.
 19. The tissue sample handlingapparatus (1) according to claim 18, wherein an open- or closed-loopcontrol apparatus controls in open- and/or closed-loop fashion at leastone of the following in accordance with the information ascertained bythe image processing system (18): the sample holding position, a traveldistance of the sample holding position, a position of the aspirationnozzle (3), a travel distance of the aspiration nozzle (3), and thenegative pressure.
 20. An automatic handling machine or automatic samplepreparation machine having a tissue sample handling apparatus (1)according to claim 18.